Prostate cancer will affect one in every six men during their lifetime, with over 200,000 diagnoses and 30,000 deaths per year in the U.S. alone (1). It is the second leading cause of death due to cancer in men. Current screening methods for prostate cancer include the prostate-specific antigen (PSA) test, which detects the levels of prostate-specific antigen in a blood sample, and digital rectal examination (DRE). Although 60 to 70% of at-risk men in the U.S. have undergone PSA testing since the test was adopted, prostate cancer death rates have only slightly decreased. This is largely due to two reasons: 1) the fact that PSA testing fails to identify a subset of aggressive cancers, and 2) that only about 30% of men with a positive PSA test have a positive biopsy. Diagnosis is further complicated by the fact that of all men treated for prostate cancer, about 25% have disease recurrence and require additional treatment, while in other cases some tumors never progress at all and may be better left untreated. Therefore, a key issue with prostate cancer diagnosis today is the inability to predict the course of the disease. Together, these statistics have made prostate screening with conventional methods a controversial issue. The ideal prostate cancer biomarker(s) would therefore be suitable for early detection, as well as have the ability to predict disease aggressiveness and ideally to be able to monitor disease progression during therapy or post surgery.
Currently, PSA is recognized as the best available serum marker for prostate cancer, however, there is substantial room for improvement. The impact of PSA testing, beginning in the early 1990s, can be seen by decreases in the numbers of men diagnosed with metastasis, concurrent with overall decreased mortality (2). However, this may be due to the fact that PSA screening increased awareness of prostate cancer, which ultimately stimulated the analysis of more biopsies. Calculating the performance characteristics (sensitivity and specificity) of the PSA test is difficult because of ethnicity-related difference in incidence, and that in most studies, the percentage of biopsies performed is higher than what would normally be performed in clinical practice. In the Prostate Cancer Prevention Trial (PCPT) (3), the false-negative rate for detection of high-grade tumors was at least 15%, with a false-positive rate of 70% (i.e. only 30% of men with elevated PSA have a positive biopsy). In another study, the Physician's Health Study (4), the sensitivity for aggressive cancer over a four-year period was 87%, but dropped to 53% for non-aggressive cancers. There have been many other studies carried out to assess PSA sensitivity, but the latest findings claim overall sensitivity to be at best 73% (5). Lowering the PSA threshold would detect more cancers, but at the cost of more false-positives and subsequently more biopsies. To complicate matters further, it appears that due to increased prevalence of benign prostatic hyperplasia (BPH) in the ageing male population, the sensitivity of the PSA test with a cut-point of 4 ng/ml decreases with age.
PSA alone cannot diagnose prostate cancer. Diagnosis is a complex process, which involves integrating the results of a physical examination, a PSA test, the Gleason grade (by assessing glandular architecture at biopsy) and possibly other lab tests.
It is clear that there is a need for improving prostate cancer detection. A test that is able to detect risk for, or the presence of, prostate cancer or that can predict aggressive disease with high specificity and sensitivity would be very beneficial and would impact prostate cancer morbidity. The claimed invention describes the discovery of molecules present in serum samples which show a differential pattern of abundances between prostate cancer patients and normal individuals.